NURS 6521 Discussion: Comparing and Contrasting Pharmacologic Options for the Treatment of Generalized Anxiety Disorder

Generalized anxiety disorder is a chronic condition characterized by uncontrollable worrying, and of all anxiety disorders, GAD is the most least likely to remit (Rosenthal & Burchum, 2021). Depression is usually associated with GAD. According to Rosenthal & Burchum (2021), the hallmark of GAD is unrealistic or excessive anxiety about several events or activities. The FDA approved first-line medication choices include SSRI’s, SNRI’s and buspirone. The approved second line of medication is benzodiazepine. Antidepressants have a delay effect which can take several weeks to take effect, while benzodiazepine’s onset is rapid. The four main first-line medications include SSRI – Paroxetine (Paxil) & Escitalopram (Lexapro), SNRI – Venlafaxine (Effexor XR) & Duloxetine (Cymbalta).

Pharmacodynamics for SSRI’s according to Rosenthal & Burchum (2021), is by selectively blocking neuronal reuptake of serotonin 5-HT, a monoamine neurotransmitter. The reuptake concent

NURS 6521 Discussion Comparing and Contrasting Pharmacologic Options for the Treatment of Generalized Anxiety Disorder

ration of 5-HT in the synapse increases, which activates the postsynaptic 5-ht receptors, this mechanism which is consistent with the theory that depression stems from a deficiency in monoamine-mediated transmission (Rosenthal & Burchum, 2021).

–

Pharmacokinetics for SSRI’s, oral medication is well absorbed, even in the presence of food. They are metabolized by the liver primarily by CYP2D6, then followed by excretion in the urine (Rosenthal & Burchum, 2021). SSRI’s are known to cause sexual dysfunction including impotence and delayed orgasm, delayed ejaculation and decreased sexual interest. Weight gain is also associated with SSRI’s possibly due to the decreased sensitivity of 5-HT receptors that regulate appetite (Rosenthal & Burchum, 2021). MAOI’s are to be avoided when taking SSRI’s due to the risk of serotonin syndrome, which can be life threatening if left untreated.

Click here to ORDER an A++ paper from our MASTERS and DOCTORATE WRITERS: NURS 6521 Discussion: Comparing and Contrasting Pharmacologic Options for the Treatment of Generalized Anxiety Disorder

Pharmacodynamics for SNRI’s block the neuronal reuptake of serotonin and norepinephrine, with minimal effects of

NURS 6521 Discussion Comparing and Contrasting Pharmacologic Options for the Treatment of Generalized Anxiety Disorder

other transmitters or receptors (Rosenthal & Burchum, 2021). The drug produces a powerful blockade of NE and 5HT reuptake and weak blockade of dopamine reuptake. There is evidence that SSRI’s are tolerated and considered safer to take.

–

Pharmacokinetics for SNRI’s, orally they are well absorbed. The liver converts the medication to desvenlafaxine and active metabolite. The half-life is 5 hours for the parent drug and 11 hours for the active metabolite (Rosenthal & Burchum, 2021). SNRI’s are also known to cause sexual dysfunction. In addition, monitoring blood pressure is needed due to dose related diastolic hypertension. The patient will need to have their sodium levels monitored especially if taking a diuretic which will increase the chance of hyponatremia. As with SSRI’s MAOI’s will need to be avoided due to the risk of serotonin syndrome.

–

In comparison according to Jakuboyski et al, (2018), higher doses of SSRIs within the therapeutic range are associated with greater treatment benefit, whereas higher doses of SNRIs are not.

–

According to Ruhe et al, (2019), Because the prevalence of antidepressant withdrawal symptoms is unknown and not all patients require dose reductions to discontinue antidepressants, three risk-factors that are consistently reported in the literature to indicate an increased risk of antidepressant withdrawal symptoms: (1) dosing above the minimal effective dose to reach efficacy, (2) antidepressant withdrawal symptoms when a dose was missed or during strategic treatment interruption, and (3) earlier failed attempts to discontinue the SSRI or SNRI.

–

Benzodiazepine, though the second line in treatment for anxiety due to the risk of dependence, is the first line for an acute anxiety attack. According to Rosenthal & Burchum (2021), benefits derive from enhancing responses to GABA, an inhibitory neurotransmitter. Benzodiazepines should be avoided in patients with a known history of drug abuse.

References

–

Jakubovski, E., Johnson, J. A., Nasir, M., Müller-Vahl, K., & Bloch, M. H. (2018). Systematic Review and meta-analysis: Dose-response curve of ssris and Snris in anxiety disorders. Depression and Anxiety, 36(3), 198–212. https://doi.org/10.1002/da.22854

–

Rosenthal, L. D., & Burchum, J. R. (2021). Lehnes pharmacotherapeutics for advanced practice nurses and physician assistants. St. Louis, MO: Elsevier.

–

Ruhe, H. G., Horikx, A., van Avendonk, M. J., Groeneweg, B. F., & Woutersen-Koch, H. (2019). Tapering of SSRI treatment to mitigate withdrawal symptoms. The Lancet Psychiatry, 6(7), 561–562. https://doi.org/10.1016/s2215-0366(19)30182-8

Generalized anxiety disorder (GAD) is a long-term condition characterized by excessive or exaggerated anxiety and fear of life events for no apparent reason. Treatment for GAD can be anything from counseling to medications like antidepressants and anxiolytics. Physicians prescribe anxiolytics to stop or prevent anxiety symptoms through quieting nerve cell activity in the brain (Bandelow et al., 2017). Treatment choices for GAD are based on how significant the problem is affecting the ability of the patient’s body to carry out daily activities. The main treatment options for GAD are Medications or pharmacology, and psychotherapy (Robichaud et al., 2019).

Short-term drugs for episodic anxiety symptoms help for transitioning to other anti-anxiety drugs including antidepressants like the serotonin-norepinephrine reuptake inhibitor (SNRI), selective serotonin reuptake inhibitor (SSRI), and tricyclic antidepressant (TCA). Antidepressants are often used as the first-line treatment for GAD because of their mechanism of action with the downregulation of noradrenalinergic receptors. Also, unlike benzodiazepines, it may be used without causing tolerance. The pharmacodynamic effects of FDA-approved drugs depend on the class to which they belong. Benzodiazepines bind to the gamma aminobutyric acid (GABA) receptors of the brain and enhance the GABA-medicated synaptic inhibition hence lowering abnormal excitement of the brain (Beck & Beck, 2018).

Pharmacokinetically, diazepam is rapidly absorbed orally and is widely bound and distributed to plasma proteins, where it is metabolized by cytochrome p450 enzymes, bound to glucuronide, and excreted in the urine. Many traditional diazepines are metabolized in the liver and, when combined with drugs that block their effects, increase blood levels and can cause side effects. Examples include alprazolam and clonazepam. Another class of drug is buspirone, whose effects are related to the neurotransmitter serotonin. Unlike diazepam, it promotes noradrenalinergic and dopaminergic cell firing while having different effects on serotonergic activity. Therefore, their mechanism of action rejects the notion that there is only one neurotransmitter that mediates fear. It is orally absorbed, bound to serum albumin, distributed, metabolized in the liver, and then excreted in the urine. The third class is Vistaril. It works by blocking histamine receptors and treating insomnia GAD. It falls into any histamine class and can be administered as an oral capsule/tablet or an injectable liquid. The drug is rapidly absorbed in the gastrointestinal tract and its effects are notable within the first thirty minutes. Despite its rapid action it is often associated with a lot of sedation (Beck & Beck, 2018). Among the pharmacotherapeutic options for treating GAD are antidepressants including the SSRIs e.g., Lexapro and Paxil, and SNRIs such as Duloxetine and venlafaxine. Alternatively, physicians may consider cognitive psychological counseling depending on contraindications based on the genetic predisposition of the patient, age, or situation.

References

Bandelow, B., Michaelis, S., & Wedekind, D. (2017). Treatment of anxiety disorders. Dialogues in clinical neuroscience, 19(2), 93. Doi: 10.31887/DCNS.2017.19.2/bbandelow

Beck, D. A., & Beck, C. L. (2018). Anxiolytics. In Clinical Psychopharmacology for Neurologists (pp. 73-95).

Robichaud, M., Koerner, N., & Dugas, M. J. (2019). Cognitive behavioral treatment for generalized anxiety disorder: From science to practice. Routledge. https://www.taylorfrancis.com/books/mono/10.4324/9781315709741/cognitivebehavioral-treatment-generalized-anxiety-disorder-melisa-robichaud-naomi-koernermichel-dugas

Week 8 Discussion

COLLAPSE

Pharmacokinetics is the study of drug movement throughout the body. There are four basic pharmacokinetic processes: absorption, distribution, metabolism, and excretion. Pharmacodynamics is the study of the biochemical and physiologic effects of drugs in the body (Rosenthal, L. D., & Burchum, J, R. 2021 pg. 13 & 22). Generalized anxiety disorder is chronic condition that is uncontrollable worrying. Most patients with this disorder also have another psychotic disorder called depression. The hallmark of GAD is unrealistic or excessive anxiety about several events or activities that last 6 months or longer (Rosenthal, L. D., & Burchum, J, R. 2021 pg. 243). Treatments used for this disorder can be nondrug or drug therapy. The non-drug approach could be supportive therapy, cognitive behavioral therapy, biofeedback, or relaxation therapy. All these therapies can help with coping skills with anxiety provoking situations (Rosenthal, L. D., & Burchum, J, R. 2021 pg. 243). If drugs are needed the 1^st line are SRRI and SNRI which the most used are Cymbalta, Paxil, Lexapro, Effexor XL. The 2^nd line benzodiazepines are used for immediate stabilization when anxiety is severe. Buspirone is used as benzo (McCance & Huether, pg. 605). The 1^st line drugs are used on a continuous basis with the supervision of a psychiatrist and the benzos are used for as needed purposes.

Reference:

Rosenthal, L. D., & Burchum, J. R. (2021). Lehne’s pharmacotherapeutics for advanced practice nurses and physician assistants (2^nd ed.) St. Louis, MO: Elsevier.

McCance, K. L. & Huether, S. E. (2019). Pathophysiology: The biologic basis for disease in adults and children(8th ed.). St. Louis, MO: Mosby/Elsevier

Pharmacology for Psychological Disorders

COLLAPSE

There have been several studies conducted to explore the effect of drugs on the central nervous system. The primary aim of these studies have been to establish penetration of blood-brain barrier, explore the target engagement and the mechanism involved. Anxiety disorders are the most prevalent psychiatric disorders and a leading cause of mental disability. Selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) are the first line of treatment for Generalized Anxiety Disorders (GAD). The recommended duration of treatment may vary anywhere from 3 months to 1 year or longer depending on the client’s compliance, the conditions and other influencing factors. These medications are well tolerated and the side effects and adverse effects are short lived or managed with the use of adjunctive treatment. The tricyclic antidepressants were the first classes of medications used for anxiety disorders that act as reuptake inhibitors of transporters of serotonin and norepinephrine. However despite its efficacy to SSRIs they are less prescribed due to side effects including sedation, weight gain, dry mouth, arrhythmias, and risk of mortality with overdose(Bakker, Balkom, & Spinhoven, 2002). Mixed antidepressants such as Mirtazapine has a broad pharmacological effect and Bupropion is approved for the treatment of MDD as it acts as a dopamine norepinephrine reuptake inhibitor. Although there is increasing stigma around the use of Benzodiazepines they have been a longstanding treatment for anxiety and are still widely prescribed class of psychiatric medications (Agarwal, & Landon, 2019). The most studied antihistamine is Hydroxyzine. It is the only antihistamine that has been approved by FDA for use in anxiety. Certain Beta adrenergic antagonist although not approved for any psychiatric indications has been widely prescribed for social anxiety disorder and performance anxiety. The only antipsychotic which is FDSA approved for anxiety treatment is a first generation antipsychotic, trifluoperazine.

References

Agarwal, S. D., & Landon, B. E. (2019). Patterns in Outpatient Benzodiazepine Prescribing in the United States. JAMA Network Open, 2(1), e187399. https://doi.org/10.1001/jamanetworkopen.2018.7399

Bakker, A., van Balkom, A. J. L. M., & Spinhoven, P. (2002). SSRIs vs. TCAs in the treatment of panic disorder: a meta-analysis. Acta Psychiatrica Scandinavica, 106(3), 163–167. https://doi.org/10.1034/j.1600-0447.2002.02255.x

Garakani, A., Murrough, J. W., Freire, R. C., Thom, R. P., Larkin, K., Buono, F. D., & Iosifescu, D. V. (2020). Pharmacotherapy of Anxiety Disorders: Current and Emerging Treatment Options. Frontiers in Psychiatry, 11. https://doi.org/10.3389/fpsyt.2020.595584

NURS 6521 Discussion: Comparing and Contrasting Pharmacologic Options for the Treatment of Generalized Anxiety Disorder